BTX-A51 in Patients With Liposarcoma or CIC-rearranged Sarcoma

This is a two-cohort, pilot study assessing the safety and preliminary exploration of BTX-A51 at two dose levels in participants with metastatic and/or recurrent liposarcomas characterized by Murine Double Minute Clone 2 (MDM2) amplifications (i.e. de-differentiated and /or well-differentiated liposarcomas), myxoid liposarcoma, and CIC-rearranged sarcomas. BTX-A51 works in a different way from currently approved therapies used to treat liposarcoma by blocking proteins called CK1α and CDK9.

The U.S. Food and Drug Administration (FDA) has not approved BTX-A51 as a treatment for liposarcoma characterized by MDM2 amplifications, myxoid liposarcoma, or CIC-rearranged sarcomas.

The research study procedures include screening for eligibility, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, or Positron Emission Tomography (PET) scans, blood tests, and tumor biopsies.

Participants will receive study treatment for as long as there are no serious side effects, and disease does not get worse. Participants will be followed for 1 year after the last dose of BTX-A51.

It is expected that about 24 people will take part in this research study.

Edgewood Oncology is supporting this research study by providing the study drug.

Inclusion criteria

• Study participants must have histologically-confirmed metastatic and/or recurrent liposarcoma (limited to the subtypes of well-differentiated and/or dedifferentiated liposarcoma, which are associated with MDM2 amplifications), or myxoid liposarcoma, or CIC-rearranged sarcoma.
• ECOG performance status ≤2
• Adequate organ and marrow function as defined by the following metrics resulted within 7 days of study enrollment:

• WBC >3000/mm3
• Platelets >75,000μl
• ANC >1500μl
• Hgb >9g/dl
• Creatinine <1.5 x ULN or measured CrCl of >60ml/m2/1.73 m2
• Total bilirubin <2 x ULN
• AST/ALT <3 x ULN
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non- nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as

≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.

• Patients must have recovered from toxicity related to prior therapy to grade <=1 (defined by CTCAE v5.0) (except alopecia and neuropathy, or immunotherapy related hypothyroidism)
• As the effect of this study drug on the developing human fetus is not known, women of child-bearing potential and men must agree to use at least 2 methods of contraception (abstinence; hormonal or barrier method of birth control) for the study and at least 2 months after completion.
• Female patient of childbearing potential has a negative serum pregnancy test within 7 days of study enrollment.
• Ability to understand and the willingness to sign a written informed consent document.
• Age ≥18 years
• Patients must have completed all prior anti-cancer treatment for liposarcoma, including radiation, ≥ 14 days prior to registration.

Exclusion criteria

• Patient with current evidence of active and uncontrolled infection, NYHA Class III-IV CHF, documented Child's class B-C cirrhosis, or uncontrolled medical disease which in the opinion of the investigator or the sponsor could compromise safety and/or assessment of efficacy.
• Active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV); subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative PCR result before enrollment; those who are PCR positive will be excluded.
• Major surgical procedure or open surgical biopsy within 28 days of first dose of study drug
• Active central nervous system (CNS) disease involvement, or prior history of NCI CTCAE Grade ≥3 drug-related CNS toxicity. Subject with known CNS metastases that are treated and stable (without evidence of CNS toxicity) and are not requiring systemic steroids are allowed to be enrolled.
• Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Myocardial infarction within 12 months of screening
• Use of any other concurrent investigational agents or anticancer agents, excluding hormonal therapy for breast or prostate cancer
• Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BTX- A51, breastfeeding should be discontinued if the mother is treated with BTX-A51.
• Inability to swallow pills or inadequate GI absorption in the opinion of the treating investigator.